Method and apparatus for interlocking stimulation parameters for neuromodulation

ABSTRACT

An example of a system for delivering neurostimulation may include a display and an interface control circuit. The interface control circuit may be configured to define a stimulation waveform according to which the neurostimulation is delivered. The stimulation waveform is defined by waveform parameters including one or more user-adjustable parameters. The interface control circuit may include a parameter selector, an effect analyzer, and a parameter generator. The parameter selector may be configured to present values for each user-adjustable parameter on the display and allow the user to select a value for each user-adjustable parameter from the presented values. The effect analyzer may be configured to estimate an interactive effect of different stimuli of the neurostimulation. The parameter generator may be configured to select a rate rule based on the estimated interactive effect and to generate the values for each user-adjustable parameter according to the selected rate rule.

CLAIM OF PRIORITY

This application claims the benefit of priority under 35 U.S.C. §119(e)of U.S. Provisional Patent Application Ser. No. 62/310,306, filed onMar. 18, 2016, which is herein incorporated by reference in itsentirety.

TECHNICAL FIELD

This document relates generally to neurostimulation and moreparticularly to a system that interlocks stimulation parameters forprogramming stimulation devices for neuromodulation.

BACKGROUND

Neurostimulation, also referred to as neuromodulation, has been proposedas a therapy for a number of conditions. Examples of neurostimulationinclude Spinal Cord Stimulation (SCS), Deep Brain Stimulation (DBS),Peripheral Nerve Stimulation (PNS), and Functional ElectricalStimulation (FES). Implantable neurostimulation systems have beenapplied to deliver such a therapy. An implantable neurostimulationsystem may include an implantable neurostimulator, also referred to asan implantable pulse generator (IPG), and one or more implantable leadseach including one or more electrodes. The implantable neurostimulatordelivers neurostimulation energy through one or more electrodes placedon or near a target site in the nervous system. An external programmingdevice is used to program the implantable neurostimulator withstimulation parameters controlling the delivery of the neurostimulationenergy.

In one example, the neurostimulation energy is delivered in the form ofelectrical neurostimulation pulses. The delivery is controlled usingstimulation parameters that specify spatial (where to stimulate),temporal (when to stimulate), and informational (signals directing thenervous system to respond as desired) aspects of a pattern ofneurostimulation pulses. The human nervous systems use neural signalshaving sophisticated shapes and patterns to communicate various types ofinformation, including sensations of pain, pressure, temperature, etc.It may interpret an artificial stimulation with a simple pattern ofstimuli as an unnatural phenomenon, and respond with an unintended andundesirable sensation, response, and/or movement. Also, as the conditionof the patient may change while receiving a neurostimulation therapy,the characteristic of the neurostmulation energy applied to the patientmay need to be changed to maintain efficacy of the therapy whileminimizing the unintended and/or undesirable sensation, response, and/ormovement. While modern electronics can accommodate the need forgenerating sophisticated signals that emulate natural patterns of neuralsignals observed in the human body, the capability of a neurostimulationsystem depends on its post-manufacturing programmability to a greatextent. For example, a sophisticated pulse pattern may only benefit apatient when it is customized for that patient, with potentialinteractions between neurostimulation pulses controlled to ensuretherapy efficacy and safety. This makes programming of a stimulationdevice for a patient a challenging task.

SUMMARY

An example (e.g., “Example 1”) of a system for deliveringneurostimulation to a patient and controlling the delivery of theneurostimulation by a user is provided. The system may include a displayand an interface control circuit. The interface control circuit may beconfigured to define a stimulation waveform according to which theneurostimulation is to be delivered. The stimulation waveform is definedby a plurality of waveform parameters including one or moreuser-adjustable parameters. The interface control circuit may include aparameter selector, an effect analyzer, and a parameter generator. Theparameter selector may be configured to present a plurality of valuesfor each parameter of the one or more user-adjustable parameters on thedisplay and allow the user to select a value for each parameter from thepresented plurality of values. The effect analyzer may be configured toestimate an interactive effect of different stimuli of theneurostimulation. The parameter generator may be configured to select arate rule from a plurality of rate rules based on the estimatedinteractive effect and to generate the plurality of values for eachparameter of the one or more user-adjustable parameters according to theselected rate rule.

In Example 2, the subject matter of Example 1 may optionally beconfigured such that the effect analyzer is configured to determinevolumes of tissue activated (VTAs) each associated with a stimulus ofthe different stimuli of the neurostimulation, and the parametergenerator is configured to select the rate rule from the plurality ofrate rules based on the VTAs.

In Example 3, the subject matter of any one or a combination of Examples1 and 2 may optionally be configured to further include a programmingcontrol circuit and a user interface. The programming control circuit isconfigured to generate a plurality of stimulation parameters controllingdelivery of the neurostimulation according to the stimulation waveform.The user interface includes the display and the interface controlcircuit.

In Example 4, the subject matter of any one or a combination of Examples1 and 2 may optionally be configured such that the parameter selector isconfigured to present the plurality of values for each parameter of theone or more user-adjustable parameters on the display as one or morevalue ranges and allow the user to select a value for each parameterfrom the one or more value ranges.

In Example 5, the subject matter of any one or any combination ofExamples 1 to 4 may optionally be configured such that the effectanalyzer is configured to determine the VTAs using one or morebiological models.

In Example 6, the subject matter of any one or any combination ofExamples 1 to 5 may optionally be configured such that the effectanalyzer is configured to determine the VTAs using stimulation fieldmodels (SFMs).

In Example 7, the subject matter of any one or a combination of Examples5 and 6 may optionally be configured such that the effect analyzer isconfigured to determine the VTAs using patient-specific informationrelated to one or more of size, shape, location, extent, or distributionof each of the VTAs.

In Example 8, the subject matter of any one or any combination ofExamples 1 to 7 may optionally be configured such that the parametergenerator is configured to generate the plurality of values for eachparameter of the one or more user-adjustable parameters such that theVTAs do not spatially overlap.

In Example 9, the subject matter of any one or any combination ofExamples 1 to 7 may optionally be configured such that the parametergenerator is configured to generate the plurality of values for eachparameter of the one or more user-adjustable parameters such that theVTAs have an overlapping volume that is within a specified range.

In Example 10, the subject matter of any one or any combination ofExamples 1 to 7 may optionally be configured such that the parametergenerator is configured to generate the plurality of values for eachparameter of the one or more user-adjustable parameters for controllingan extent to which a common anatomical target indicated by the VTAs ismodulated by the different stimuli of the neurostimulation.

In Example 11, the subject matter of any one or any combination ofExamples 1 to 7 may optionally be configured such that the parametergenerator is configured to generate the plurality of values for eachparameter of the one or more user-adjustable parameters for controllingan extent to which a common neural element indicated by the VTAs ismodulated by the different stimuli of the neurostimulation.

In Example 12, the subject matter of any one or any combination ofExamples 1 to 7 may optionally be configured such that the parametergenerator is configured to generate the plurality of values for eachparameter of the one or more user-adjustable parameters for controllingan extent to which a common downstream tissue target indicated by theVTAs is modulated by the different stimuli of the neurostimulation.

In Example 13, the subject matter of any one or any combination ofExamples 1 to 7 may optionally be configured such that the parametergenerator is configured to generate the plurality of values for eachparameter of the one or more user-adjustable parameters for controllingan extent to which a common physiological target indicated by the VTAsis modulated by the different stimuli of the neurostimulation.

In Example 14, the subject matter of any one or any combination ofExamples 1 to 13 may optionally be configured such that the parameterselector includes a frequency selector configured to allow to user toselect a stimulation frequency from a plurality of stimulationfrequencies.

In Example 15, the subject matter of any one or any combination ofExamples 1 to 7 may optionally be configured such that the frequencyselector is configured to present on the display a plurality ofstimulation frequencies associated with each area of the plurality ofareas of stimulation, and to receive a selection of a stimulationfrequency from the presented plurality of stimulation frequencies forthat area of the plurality of areas of stimulation.

An example (e.g., “Example 16”) of a method for deliveringneurostimulation to a patient is also provided. The method includesdelivering the neurostimulation according to a stimulation waveformdefined by a plurality of waveform parameters including one or moreuser-adjustable parameters, estimating an interactive effect ofdifferent stimuli of the neurostimulation, selecting a rate rule from aplurality of rate rules based on the estimated interactive effect,generating a plurality of values for each parameter of the one or moreuser-adjustable parameters according to the selected rate rule,presenting the plurality of values for each parameter of the one or moreuser-adjustable parameters on a display, and allowing a user to select avalue for each parameter of the one or more user-adjustable parametersfrom the plurality of values presented on the display.

In Example 17, the subject matter of estimating the interactive effectas found in Example 16 may optionally include determining volumes oftissue activated (VTAs) each associated with a stimulus of the differentstimuli of the neurostimulation, and selecting the rate rule comprisesselecting the rate rule from the plurality of rate rules based on theVTAs.

In Example 18, the subject matter of generating the plurality of valuesfor each parameter of the one or more user-adjustable parametersaccording to the selected rate rule as found in Example 17 mayoptionally include determining the plurality of values to control anextent to which the VTAs spatially overlap.

In Example 19, the subject matter of generating the plurality of valuesfor each parameter of the one or more user-adjustable parametersaccording to the selected rate rule as found in any one or a combinationof Examples 17 and 18 may optionally include determining the pluralityof values to control an extent to which a common target indicated by theVTAs is modulated by the different stimuli of the neurostimulation.

In Example 20, the subject matter of presenting the plurality of valuesfor each parameter as found in any one or any combination of claims 16to 19 may optionally include presenting a plurality of stimulationfrequencies and allowing the user to select the value for each parametercomprises allowing the user to select a stimulation frequency from thepresented plurality of stimulation frequencies.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the disclosure will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof, each of which are not tobe taken in a limiting sense. The scope of the present disclosure isdefined by the appended claims and their legal equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate generally, by way of example, variousembodiments discussed in the present document. The drawings are forillustrative purposes only and may not be to scale.

FIG. 1 illustrates an embodiment of a neurostimulation system.

FIG. 2 illustrates an embodiment of a stimulation device and a leadsystem, such as may be implemented in the neurostimulation system ofFIG. 1.

FIG. 3 illustrates an embodiment of a programming device, such as may beimplemented in the neurostimulation system of FIG. 1.

FIG. 4 illustrates an embodiment of an implantable pulse generator (IPG)and an implantable lead system, such as an example implementation of thestimulation device and lead system of FIG. 2.

FIG. 5 illustrates an embodiment of an IPG and an implantable leadsystem, such as the IPG and lead system of FIG. 4, arranged to provideneurostimulation to a patient.

FIG. 6 illustrates an embodiment of portions of a neurostimulationsystem.

FIG. 7 illustrates an embodiment of an implantable stimulator and one ormore leads of an implantable neurostimulation system, such as theimplantable neurostimulation system of FIG. 6.

FIG. 8 illustrates an embodiment of an external programming device of animplantable neurostimulation system, such as the implantableneurostimulation system of FIG. 6.

FIG. 9 illustrates an embodiment of portions of a circuit of a userinterface of a programming device, such as the external programmingdevice of FIG. 8.

FIG. 10 illustrates an embodiment of portions of a screen displayingstimulation frequencies for selection.

FIG. 11 illustrates an example of partially overlapping volumes oftissue activated by neurostimulation pulses delivered from differentelectrodes.

FIG. 12 illustrates an example of a common neural element stimulated byneurostimulation pulses delivered from different electrodes.

FIG. 13 illustrates an example of a common upstream or downstream targetstimulated by neurostimulation pulses delivered from differentelectrodes.

FIG. 14 illustrates an example of a common anatomical target stimulatedby neurostimulation pulses delivered from different electrodes.

FIG. 15 illustrates an embodiment of a stimulation parameter module of acircuit of a user interface, such as the circuit of FIG. 9.

FIG. 16 illustrates a flow chart of a method for determining stimulationparameter values based on estimated effects of neurostimulation pulsesdelivered through different electrodes.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings which form a part hereof, and in which is shown byway of illustration specific embodiments in which the invention may bepracticed. These embodiments are described in sufficient detail toenable those skilled in the art to practice the invention, and it is tobe understood that the embodiments may be combined, or that otherembodiments may be utilized and that structural, logical and electricalchanges may be made without departing from the spirit and scope of thepresent invention. References to “an”, “one”, or “various” embodimentsin this disclosure are not necessarily to the same embodiment, and suchreferences contemplate more than one embodiment. The following detaileddescription provides examples, and the scope of the present invention isdefined by the appended claims and their legal equivalents.

This document discusses, among other things, a neurostimulation systemwith programming rules, user interface, and other features thatfacilitate programming of stimulation devices for deliveringneuromodulation to each patient. In various embodiments, theneurostimulation system can include an implantable device configured todeliver neurostimulation (also referred to as neuromodulation) therapies(such as deep brain stimulation (DBS), spinal cord stimulation (SCS),peripheral nerve stimulation (PNS), vagus nerve stimulation (VNS), etc.)and one or more external devices configured to program the implantabledevice for its operations and monitor the performance of the implantabledevice. While DBS is discussed as a specific example, the presentsubject matter can also be applied to facilitate programming ofstimulation devices for delivering various types of neurostimulationtherapies. In general, various aspects of the present subject matter asdiscussed in this document may be applied to any medical system thatdelivers electrical stimulation to a patient in various embodiments. Itis also to be understood that various features of the neurostimulationare discussed in this documents as examples of techniques developed tosimplify and/or improve selected aspects of programming of thestimulation devices, rather than all the features needed for theprogramming.

FIG. 1 illustrates an embodiment of a neurostimulation system 100.System 100 includes electrodes 106, a stimulation device 104, and aprogramming device 102. Electrodes 106 are configured to be placed on ornear one or more neural targets in a patient. Stimulation device 104 isconfigured to be electrically connected to electrodes 106 and deliverneurostimulation energy, such as in the form of electrical pulses, tothe one or more neural targets though electrodes 106. The delivery ofthe neurostimulation is controlled by using a plurality of stimulationparameters, such as stimulation parameters specifying a pattern of theelectrical pulses and a selection of electrodes through which each ofthe electrical pulses is delivered. In various embodiments, at leastsome parameters of the plurality of stimulation parameters areprogrammable by a user, such as a physician or other caregiver whotreats the patient using system 100. Programming device 102 provides theuser with accessibility to the user-programmable parameters. In variousembodiments, programming device 102 is configured to be communicativelycoupled to stimulation device via a wired or wireless link.

In this document, a “user” includes a physician or other clinician orcaregiver who treats the patient using system 100; a “patient” includesa person who receives or is intended to receive neurostimulationdelivered using system 100. In various embodiments, the patient isallowed to adjust his or her treatment using system 100 to certainextent, such as by adjusting certain therapy parameters and enteringfeedback and clinical effects information. While neurostimulation energydelivered in the form of electrical pulses is discussed in variousportions of this document as a specific example of stimuli of theneurostimulation, various embodiments may use any type ofneurostimulation energy delivered in any type of stimuli that arecapable of modulating characteristics and/or activities in neural orother target tissue in a patient.

In various embodiments, programming device 102 includes a user interface110 that allows the user to control the operation of system 100 andmonitor the performance of system 100 as well as conditions of thepatient including responses to the delivery of the neurostimulation. Theuser can control the operation of system 100 by setting and/or adjustingvalues of the user-programmable parameters.

In various embodiments, user interface 110 includes a graphical userinterface (GUI) that allows the user to set and/or adjust the values ofthe user-programmable parameters by creating and/or editingrepresentations of various waveforms, including direct and abstractgraphical representations. Such waveforms may include, for example, awaveform representing a pattern of neurostimulation pulses to bedelivered to the patient as well as individual waveforms that are usedas building blocks of the pattern of neurostimulation pulses, such asthe waveform of each pulse in the pattern of neurostimulation pulses.The GUI may also allow the user to set and/or adjust stimulation fieldseach defined by a set of electrodes through which one or moreneurostimulation pulses represented by a waveform are delivered to thepatient. The stimulation fields may each be further defined by thedistribution of the current of each neurostimulation pulse in thewaveform. In various embodiments, neurostimulation pulses for astimulation period (such as the duration of a therapy session) may bedelivered to multiple stimulation fields.

In various embodiments, system 100 can be configured forneurostimulation applications. User interface 110 can be configured toallow the user to control the operation of system 100 forneurostimulation. For example, system 100 as well as user interface 100can be configured for DBS applications. Such DBS configuration includesvarious features that may simplify the task of the user in programmingstimulation device 104 for delivering DBS to the patient, such as thefeatures discussed in this document.

FIG. 2 illustrates an embodiment of a stimulation device 204 and a leadsystem 208, such as may be implemented in neurostimulation system 100.Stimulation device 204 represents an embodiment of stimulation device104 and includes a stimulation output circuit 212 and a stimulationcontrol circuit 214. Stimulation output circuit 212 produces anddelivers neurostimulation pulses. Stimulation control circuit 214controls the delivery of the neurostimulation pulses from stimulationoutput circuit 212 using the plurality of stimulation parameters, whichspecifies a pattern of the neurostimulation pulses. Lead system 208includes one or more leads each configured to be electrically connectedto stimulation device 204 and a plurality of electrodes 206 distributedin the one or more leads. The plurality of electrodes 206 includeselectrode 206-1, electrode 206-2, . . . electrode 206-N, each a singleelectrically conductive contact providing for an electrical interfacebetween stimulation output circuit 212 and tissue of the patient, whereN≧2. The neurostimulation pulses are each delivered from stimulationoutput circuit 212 through a set of electrodes selected from electrodes206. In various embodiments, the neurostimulation pulses may include oneor more individually defined pulses, and the set of electrodes may beindividually definable by the user for each of the individually definedpulses or each of collections of pulse intended to be delivered usingthe same combination of electrodes. In various embodiments, one or moreadditional electrodes 207 (each of which may be referred to as areference electrode) can be electrically connected to stimulation device204, such as one or more electrodes each being a portion of or otherwiseincorporated onto a housing of stimulation device 204. Monopolarstimulation uses a monopolar electrode configuration with one or moreelectrodes selected from electrodes 206 and at least one electrode fromelectrode(s) 207. Bipolar stimulation uses a bipolar electrodeconfiguration with two electrodes selected from electrodes 206 and noneelectrode(s) 207. Multipolar stimulation uses a multipolar electrodeconfiguration with multiple (two or more) electrodes selected fromelectrodes 206 and none of electrode(s) 207.

In various embodiments, the number of leads and the number of electrodeson each lead depend on, for example, the distribution of target(s) ofthe neurostimulation and the need for controlling the distribution ofelectric field at each target. In one embodiment, lead system 208includes 2 leads each having 8 electrodes.

FIG. 3 illustrates an embodiment of a programming device 302, such asmay be implemented in neurostimulation system 100. Programming device302 represents an embodiment of programming device 102 and includes astorage device 318, a programming control circuit 316, and a userinterface 310. Storage device 318 stores one or more stimulationwaveforms each represent a pattern of neurostimulation pulses to bedelivered during a stimulation period. Programming control circuit 316generates the plurality of stimulation parameters that controls thedelivery of the neurostimulation pulses according to at least one of thestored one or more stimulation waveforms. User interface 310 representsan embodiment of user interface 110 and includes neurostimulationmodules 320. In various embodiments, neurostimulation modules 320 areeach configured to support one or more functions that facilitateprogramming of stimulation devices, such as stimulation device 104including its various embodiments as discussed in this document, fordelivering neurostimulation to each patient with safe and efficacioussettings. Examples of such one or more functions are discussed belowwith references to FIG. 9.

In various embodiments, user interface 310 allows for definition of apattern of neurostimulation pulses for delivery during aneurostimulation therapy session by creating and/or adjusting one ormore stimulation waveforms using a graphical method. The definition canalso include definition of one or more stimulation fields eachassociated with one or more pulses in the pattern of neurostimulationpulses. In various embodiments, user interface 310 includes a GUI thatallows the user to define the pattern of neurostimulation pulses andperform other functions using graphical methods. In this document,“neurostimulation programming” can include the definition of the one ormore stimulation waveforms, including the definition of one or morestimulation fields.

In various embodiments, circuits of neurostimulation 100, including itsvarious embodiments discussed in this document, may be implemented usinga combination of hardware and software. For example, the circuit of userinterface 110, stimulation control circuit 214, programming controlcircuit 316, and neurostimulation modules 320, including their variousembodiments discussed in this document, may be implemented using anapplication-specific circuit constructed to perform one or moreparticular functions or a general-purpose circuit programmed to performsuch function(s). Such a general-purpose circuit includes, but is notlimited to, a microprocessor or a portion thereof, a microcontroller orportions thereof, and a programmable logic circuit or a portion thereof.

FIG. 4 illustrates an embodiment of an implantable pulse generator (IPG)404 and an implantable lead system 408. IPG 404 represents an exampleimplementation of stimulation device 204. Lead system 408 represents anexample implementation of lead system 208. As illustrated in FIG. 4, IPG404 that can be coupled to implantable leads 408A and 408B at a proximalend of each lead. The distal end of each lead includes electricalcontacts or electrodes 406 for contacting a tissue site targeted forelectrical neurostimulation. As illustrated in FIG. 1, leads 408A and408B each include 8 electrodes 406 at the distal end. The number andarrangement of leads 408A and 408B and electrodes 406 as shown in FIG. 1are only an example, and other numbers and arrangements are possible. Invarious embodiments, the electrodes are ring electrodes. The implantableleads and electrodes may be configured by shape and size to provideelectrical neurostimulation energy to a neuronal target included in thesubject's brain, or configured to provide electrical neurostimulationenergy to a nerve cell target included in the subject's spinal cord.

FIG. 5 illustrates an embodiment of an IPG 504 and an implantable leadsystem 508 arranged to provide neurostimulation to a patient. An exampleof IPG 504 includes IPG 404. An example of lead system 508 includes oneor more of leads 408A and 408B. In the illustrated embodiment,implantable lead system 508 is arranged to provide Deep BrainStimulation (DBS) to a patient, with the stimulation target beingneuronal tissue in a subdivision of the thalamus of the patient's brain.Other examples of DBS targets include neuronal tissue of the globuspallidus (GPi), the subthalamic nucleus (STN), the pedunculopontinenucleus (PPN), substantia nigra pars reticulate (SNr), cortex, globuspallidus externus (GPe), medial forebrain bundle (MFB), periaquaductalgray (PAG), periventricular gray (PVG), habenula, subgenual cingulate,ventral intermediate nucleus (VIM), anterior nucleus (AN), other nucleiof the thalamus, zona incerta, ventral capsule, ventral striatum,nucleus accumbens, and any white matter tracts connecting these andother structures.

Returning to FIG. 4, the IPG 404 can include a hermetically-sealed IPGcase 422 to house the electronic circuitry of IPG 404. IPG 404 caninclude an electrode 426 formed on IPG case 422. IPG 404 can include anIPG header 424 for coupling the proximal ends of leads 408A and 408B.IPG header 424 may optionally also include an electrode 428. Electrodes426 and/or 428 represent embodiments of electrode(s) 207 and may each bereferred to as a reference electrode. Neurostimulation energy can bedelivered in a monopolar (also referred to as unipolar) mode usingelectrode 426 or electrode 428 and one or more electrodes selected fromelectrodes 406. Neurostimulation energy can be delivered in a bipolarmode using a pair of electrodes of the same lead (lead 408A or lead408B). Neurostimulation energy can be delivered in an extended bipolarmode using one or more electrodes of a lead (e.g., one or moreelectrodes of lead 408A) and one or more electrodes of a different lead(e.g., one or more electrodes of lead 408B).

The electronic circuitry of IPG 404 can include a control circuit thatcontrols delivery of the neurostimulation energy. The control circuitcan include a microprocessor, a digital signal processor, applicationspecific integrated circuit (ASIC), or other type of processor,interpreting or executing instructions included in software or firmware.The neurostimulation energy can be delivered according to specified(e.g., programmed) modulation parameters. Examples of setting modulationparameters can include, among other things, selecting the electrodes orelectrode combinations used in the stimulation, configuring an electrodeor electrodes as the anode or the cathode for the stimulation,specifying the percentage of the neurostimulation provided by anelectrode or electrode combination, and specifying stimulation pulseparameters. Examples of pulse parameters include, among other things,the amplitude of a pulse (specified in current or voltage), pulseduration (e.g., in microseconds), pulse rate (e.g., in pulses persecond), and parameters associated with a pulse train or pattern such asburst rate (e.g., an “on” modulation time followed by an “off”modulation time), amplitudes of pulses in the pulse train, polarity ofthe pulses, etc.

FIG. 6 illustrates an embodiment of portions of a neurostimulationsystem 600. System 600 includes an IPG 604, implantable neurostimulationleads 608A and 608B, an external remote controller (RC) 632, aclinician's programmer (CP) 630, and an external trial modulator (ETM)634. IPG 404 may be electrically coupled to leads 608A and 608B directlyor through percutaneous extension leads 636. ETM 634 may be electricallyconnectable to leads 608A and 608B via one or both of percutaneousextension leads 636 and/or external cable 638. System 600 represents anembodiment of system 100, with IPG 604 representing an embodiment ofstimulation device 104, electrodes 606 of leads 608A and 608Brepresenting electrodes 106, and CP 630, RC 632, and ETM 634collectively representing programming device 102.

ETM 634 may be standalone or incorporated into CP 630. ETM 634 may havesimilar pulse generation circuitry as IPG 604 to deliverneurostimulation energy according to specified modulation parameters asdiscussed above. ETM 634 is an external device that is typically used asa preliminary stimulator after leads 408A and 408B have been implantedand used prior to stimulation with IPG 604 to test the patient'sresponsiveness to the stimulation that is to be provided by IPG 604.Because ETM 634 is external it may be more easily configurable than IPG604.

CP 630 can configure the neurostimulation provided by ETM 634. If ETM634 is not integrated into CP 630, CP 630 may communicate with ETM 634using a wired connection (e.g., over a USB link) or by wirelesstelemetry using a wireless communications link 640. CP 630 alsocommunicates with LPG 604 using a wireless communications link 640.

An example of wireless telemetry is based on inductive coupling betweentwo closely-placed coils using the mutual inductance between thesecoils. This type of telemetry is referred to as inductive telemetry ornear-field telemetry because the coils must typically be closelysituated for obtaining inductively coupled communication. IPG 604 caninclude the first coil and a communication circuit. CP 630 can includeor otherwise electrically connected to the second coil such as in theform of a wand that can be place near IPG 604. Another example ofwireless telemetry includes a far-field telemetry link, also referred toas a radio frequency (RF) telemetry link. A far-field, also referred toas the Fraunhofer zone, refers to the zone in which a component of anelectromagnetic field produced by the transmitting electromagneticradiation source decays substantially proportionally to 1/r, where r isthe distance between an observation point and the radiation source.Accordingly, far-field refers to the zone outside the boundary ofr=λ/2π, where λ is the wavelength of the transmitted electromagneticenergy. In one example, a communication range of an RF telemetry link isat least six feet but can be as long as allowed by the particularcommunication technology. RF antennas can be included, for example, inthe header of IPG 604 and in the housing of CP 630, eliminating the needfor a wand or other means of inductive coupling. An example is such anRF telemetry link is a Bluetooth® wireless link.

CP 630 can be used to set modulation parameters for the neurostimulationafter IPG 604 has been implanted. This allows the neurostimulation to betuned if the requirements for the neurostimulation change afterimplantation. CP 630 can also upload information from IPG 604.

RC 632 also communicates with IPG 604 using a wireless link 340. RC 632may be a communication device used by the user or given to the patient.RC 632 may have reduced programming capability compared to CP 630. Thisallows the user or patient to alter the neurostimulation therapy butdoes not allow the patient full control over the therapy. For example,the patient may be able to increase the amplitude of neurostimulationpulses or change the time that a preprogrammed stimulation pulse trainis applied. RC 632 may be programmed by CP 630. CP 630 may communicatewith the RC 632 using a wired or wireless communications link. In someembodiments, CP 630 is able to program RC 632 when remotely located fromRC 632.

FIG. 7 illustrates an embodiment of implantable stimulator 704 and oneor more leads 708 of an implantable neurostimulation system, such asimplantable system 600. Implantable stimulator 704 represents anembodiment of stimulation device 104 or 204 and may be implemented, forexample, as IPG 604. Lead(s) 708 represents an embodiment of lead system208 and may be implemented, for example, as implantable leads 608A and608B. Lead(s) 708 includes electrodes 706, which represents anembodiment of electrodes 106 or 206 and may be implemented as electrodes606.

Implantable stimulator 704 may include a sensing circuit 742 that isoptional and required only when the stimulator needs a sensingcapability, stimulation output circuit 212, a stimulation controlcircuit 714, an implant storage device 746, an implant telemetry circuit744, a power source 748, and one or more electrodes 707. Sensing circuit742, when included and needed, senses one or more physiological signalsfor purposes of patient monitoring and/or feedback control of theneurostimulation. Examples of the one or more physiological signalsinclude neural and other signals each indicative of a condition of thepatient that is treated by the neurostimulation and/or a response of thepatient to the delivery of the neurostimulation. Stimulation outputcircuit 212 is electrically connected to electrodes 706 through one ormore leads 708 as well as electrodes 707, and delivers each of theneurostimulation pulses through a set of electrodes selected fromelectrodes 706 and electrode(s) 707. Stimulation control circuit 714represents an embodiment of stimulation control circuit 214 and controlsthe delivery of the neurostimulation pulses using the plurality ofstimulation parameters specifying the pattern of neurostimulationpulses. In one embodiment, stimulation control circuit 714 controls thedelivery of the neurostimulation pulses using the one or more sensedphysiological signals. Implant telemetry circuit 744 providesimplantable stimulator 704 with wireless communication with anotherdevice such as CP 630 and RC 632, including receiving values of theplurality of stimulation parameters from the other device. Implantstorage device 746 stores values of the plurality of stimulationparameters. Power source 748 provides implantable stimulator 704 withenergy for its operation. In one embodiment, power source 748 includes abattery. In one embodiment, power source 748 includes a rechargeablebattery and a battery charging circuit for charging the rechargeablebattery. Implant telemetry circuit 744 may also function as a powerreceiver that receives power transmitted from an external device throughan inductive couple. Electrode(s) 707 allow for delivery of theneurostimulation pulses in the monopolar mode. Examples of electrode(s)707 include electrode 426 and electrode 418 in IPG 404 as illustrated inFIG. 4.

In one embodiment, implantable stimulator 704 is used as a masterdatabase. A patient implanted with implantable stimulator 704 (such asmay be implemented as IPG 604) may therefore carry patient informationneeded for his or her medical care when such information is otherwiseunavailable. Implant storage device 746 is configured to store suchpatient information. For example, the patient may be given a new RC 632and/or travel to a new clinic where a new CP 630 is used to communicatewith the device implanted in him or her. The new RC 632 and/or CP 630can communicate with implantable stimulator 704 to retrieve the patientinformation stored in implant storage device 746 through implanttelemetry circuit 744 and wireless communication link 640, and allow forany necessary adjustment of the operation of implantable stimulator 704based on the retrieved patient information. In various embodiments, thepatient information to be stored in implant storage device 746 mayinclude, for example, positions of lead(s) 708 and electrodes 706relative to the patient's anatomy (transformation for fusingcomputerized tomogram (CT) of post-operative lead placement to magneticresonance imaging (MRI) of the brain), clinical effects map data,objective measurements using quantitative assessments of symptoms (forexample using micro-electrode recording, accelerometers, and/or othersensors), and/or any other information considered important or usefulfor providing adequate care for the patient. In various embodiments, thepatient information to be stored in implant storage device 746 mayinclude data transmitted to implantable stimulator 704 for storage aspart of the patient information and data acquired by implantablestimulator 704, such as by using sensing circuit 742.

In various embodiments, sensing circuit 742 (if included), stimulationoutput circuit 212, stimulation control circuit 714, implant telemetrycircuit 744, implant storage device 746, and power source 748 areencapsulated in a hermetically sealed implantable housing or case, andelectrode(s) 707 are formed or otherwise incorporated onto the case. Invarious embodiments, lead(s) 708 are implanted such that electrodes 706are placed on and/or around one or more targets to which theneurostimulation pulses are to be delivered, while implantablestimulator 704 is subcutaneously implanted and connected to lead(s) 708at the time of implantation.

FIG. 8 illustrates an embodiment of an external programming device 802of an implantable neurostimulation system, such as system 600. Externalprogramming device 802 represents an embodiment of programming device102 or 302, and may be implemented, for example, as CP 630 and/or RC632. External programming device 802 includes an external telemetrycircuit 852, an external storage device 818, a programming controlcircuit 816, and a user interface 810.

External telemetry circuit 852 provides external programming device 802with wireless communication with another device such as implantablestimulator 704 via wireless communication link 640, includingtransmitting the plurality of stimulation parameters to implantablestimulator 704 and receiving information including the patient data fromimplantable stimulator 704. In one embodiment, external telemetrycircuit 852 also transmits power to implantable stimulator 704 throughan inductive couple.

In various embodiments, wireless communication link 640 can include aninductive telemetry link (near-field telemetry link) and/or a far-fieldtelemetry link (RF telemetry link). For example, because DBS is oftenindicated for movement disorders which are assessed through patientactivities, gait, balance, etc., allowing patient mobility duringprogramming and assessment is useful. Therefore, when system 600 isintended for applications including DBS, wireless communication link 640includes at least a far-field telemetry link that allows forcommunications between external programming device 802 and implantablestimulator 704 over a relative long distance, such as up to about 20meters. External telemetry circuit 852 and implant telemetry circuit 744each include an antenna and RF circuitry configured to support suchwireless telemetry.

External storage device 818 stores one or more stimulation waveforms fordelivery during a neurostimulation therapy session, such as a DBStherapy session, as well as various parameters and building blocks fordefining one or more waveforms. The one or more stimulation waveformsmay each be associated with one or more stimulation fields and representa pattern of neurostimulation pulses to be delivered to the one or morestimulation field during the neurostimulation therapy session. Invarious embodiments, each of the one or more stimulation waveforms canbe selected for modification by the user and/or for use in programming astimulation device such as implantable stimulator 704 to deliver atherapy. In various embodiments, each waveform in the one or morestimulation waveforms is definable on a pulse-by-pulse basis, andexternal storage device 818 may include a pulse library that stores oneor more individually definable pulse waveforms each defining a pulsetype of one or more pulse types. External storage device 818 also storesone or more individually definable stimulation fields. Each waveform inthe one or more stimulation waveforms is associated with at least onefield of the one or more individually definable stimulation fields. Eachfield of the one or more individually definable stimulation fields isdefined by a set of electrodes through a neurostimulation pulse isdelivered. In various embodiments, each field of the one or moreindividually definable fields is defined by the set of electrodesthrough which the neurostimulation pulse is delivered and a currentdistribution of the neurostimulation pulse over the set of electrodes.In one embodiment, the current distribution is defined by assigning afraction of an overall pulse amplitude to each electrode of the set ofelectrodes. In another embodiment, the current distribution is definedby assigning an amplitude value to each electrode of the set ofelectrodes. For example, the set of electrodes may include 2 electrodesused as the anode and an electrode as the cathode for delivering aneurostimulation pulse having a pulse amplitude of 4 mA. The currentdistribution over the 2 electrodes used as the anode needs to bedefined. In one embodiment, a percentage of the pulse amplitude isassigned to each of the 2 electrodes, such as 75% assigned to electrode1 and 25% to electrode 2. In another embodiment, an amplitude value isassigned to each of the 2 electrodes, such as 3 mA assigned to electrode1 and 1 mA to electrode 2. Control of the current in terms ofpercentages allows precise and consistent distribution of the currentbetween electrodes even as the pulse amplitude is adjusted. It is suitedfor thinking about the problem as steering a stimulation locus, andstimulation changes on multiple contacts simultaneously to move thelocus while holding the stimulation amount constant. Control anddisplaying the total current through each electrode in terms of absolutevalues (e.g. mA) allows precise dosing of current through each specificelectrode. It is suited for changing the current one contact at a time(and allows the user to do so) to shape the stimulation like a piece ofclay (pushing/pulling one spot at a time).

Programming control circuit 816 represents an embodiment of programmingcontrol circuit 316 and generates the plurality of stimulationparameters, which is to be transmitted to implantable stimulator 704,based on the pattern of neurostimulation pulses as represented by one ormore stimulation waveforms. The pattern may be created and/or adjustedby the user using user interface 810 and stored in external storagedevice 818. In various embodiments, programming control circuit 816 cancheck values of the plurality of stimulation parameters against safetyrules to limit these values within constraints of the safety rules. Inone embodiment, the safety rules are heuristic rules.

User interface 810 represents an embodiment of user interface 310 andallows the user to define the pattern of neurostimulation pulses andperform various other monitoring and programming tasks. User interface810 includes a display screen 856, a user input device 858, and aninterface control circuit 854. Display screen 856 may include any typeof interactive or non-interactive screens, and user input device 858 mayinclude any type of user input devices that supports the variousfunctions discussed in this document, such as touchscreen, keyboard,keypad, touchpad, trackball, joystick, and mouse. In one embodiment,user interface 810 includes a GUI with an interactive screen thatdisplays a graphical representation of a stimulation waveform and allowsthe user to adjust the waveform by graphically editing the waveformand/or various building blocks of the waveform. The GUI may also allowthe user to perform any other functions discussed in this document wheregraphical editing is suitable as may be appreciated by those skilled inthe art.

Interface control circuit 854 controls the operation of user interface810 including responding to various inputs received by user input device858 and defining the one or more stimulation waveforms. Interfacecontrol circuit 854 includes neurostimulation modules 320.

In various embodiments, external programming device 802 has operationmodes including a composition mode and a real-time programming mode.Under the composition mode (also known as the pulse pattern compositionmode), user interface 810 is activated, while programming controlcircuit 816 is inactivated. Programming control circuit 816 does notdynamically updates values of the plurality of stimulation parameters inresponse to any change in the one or more stimulation waveforms. Underthe real-time programming mode, both user interface 810 and programmingcontrol circuit 816 are activated. Programming control circuit 816dynamically updates values of the plurality of stimulation parameters inresponse to changes in the set of one or more stimulation waveforms, andtransmits the plurality of stimulation parameters with the updatedvalues to implantable stimulator 704.

FIG. 9 illustrates an embodiment of neurostimulation modules 920, whichrepresent an embodiment of neurostimulation modules 320. In theillustrated embodiment, neurostimulation modules 920 includes astimulation parameter module 960. In various embodiments,neurostimulation modules 920 may include one or more other functionalmodules configured to be used in programming a stimulation device forneurostimulation. Examples of such functional modules are discussed inU.S. Provisional Patent Application No. 62/150,935, entitled “METHOD ANDAPPARATUS FOR PROGRAMMING DEEP BRAIN STIMULATION DEVICES”, filed on Apr.22, 2015 and U.S. Provisional Patent Application No. 62/273,508,entitled “METHODS AND SYSTEMS FOR PROGRAMMING NEUROMODULATION DEVICES”,filed on Dec. 31, 2015, both assigned to Boston ScientificNeuromodulation Corporation, which are incorporated herein by referencein their entirety. In various embodiments, such functional modules maybe used individually or in any combination to facilitate the process ofdefining the one or more stimulation waveforms, and hence the pluralityof stimulation parameters, that represent the pattern ofneurostimulation pulses to be delivered to the patient during aneurostimulation therapy session.

In the illustrated embodiment, stimulation parameter module 960 includesa frequency selector 962 that allows the user to control stimulationfrequency (also referred to as rate) at which the neurostimulationpulses are delivered. In various embodiments, frequency selector 962allows the user to select between a single frequency mode and a multiplefrequency mode. Under the single frequency mode, an adjustment ofstimulation frequency in one area of stimulation (e.g., one stimulationfield) causes an equivalent change in the stimulation frequency in allthe areas of stimulation (e.g., all the stimulation fields) in aneurostimulation session, such that only one stimulation frequency isused at a time. Under the multiple frequency mode, an adjustment ofstimulation frequency in one area of stimulation (e.g., one stimulationfield) affects the stimulation frequency associated with that area onlyand does not cause change in the stimulation frequency for another area(e.g., another stimulation field) in a neurostimulation therapy session.In various embodiments that use multiple areas of stimulations in aneurostimulation therapy session, frequency selector 962 computescompatible rates for each area of stimulation and displays them in oneor more stimulation rate tables on display screen 856. The compatible(or available) rates for an area of stimulation are stimulationfrequencies available for use based on the neurostimulation pulsesdelivered to all the areas of stimulation. The incompatible (orunavailable) rates may also be displayed, but are not selectable foruse. An example of the incompatible rates includes stimulationfrequencies at which two or more pulses of the neurostimulation pulseswill be delivered to different areas of stimulation simultaneously(i.e., at least partially overlapping in time). Simultaneous delivery ofstimulation pulses may decrease therapeutic effectiveness of theneurostimulation.

FIG. 10 illustrates an embodiment of portions of display screen 856displaying an example of such a stimulation rate table (also referred toas stimulation frequency table) 1072. Stimulation rate table 1072 isdiscussed as a specific example of present stimulation frequencies forselection. In various embodiments, the stimulation frequencies can bepresented on a display in any manner.

Stimulation rate table 1072 presents stimulation frequencies (i.e.,rates) for an area of stimulation. In various embodiments, frequencyselector 962 limits the stimulation frequencies according to acumulative rate per lead rule. Under the cumulative rate per lead rule,the user can select any stimulation frequency (i.e., rate) for the areasof stimulation (field) corresponding to a given lead such that the sumof the stimulation frequencies associated with that lead is below athreshold, which may be specified based on safety considerations. Anexample of the threshold is about 255 Hz. In various embodiments, thethreshold may be determined based on data from safety studies. Invarious other embodiments, the cumulative rate (sum of the stimulationfrequencies) may be limited for each electrode or a set of electrodes.

When operating in the multiple frequency mode, it may be desirable toprevent pulses from different timing channels from being deliveredsimultaneously (such that two or more pulses overlap in time). Thetiming channels each identify a set of one or more electrodes selectedto synchronously source or sink current to create an electric field inthe tissue to be stimulated. Amplitudes and polarities of electrodes ona channel may vary. In particular, the electrodes can be selected to bepositive (anode, sourcing current), negative (cathode, sinking current),or off (no current) polarity in any of the timing channels. In oneembodiment, frequency selector 962 provides for (1) a limitation option,in which the available combinations of stimulation frequencies arelimited, or (2) an arbitration option, in which timing of delivery ofneurostimulation pulses from a timing channel can be slightly modified(e.g., delayed) when needed, introducing some variability in theinter-pulse interval (IPI) for that timing channel. In one embodiment,stimulation frequency module 966 allows the user to select between thelimiting and arbitration options, i.e., (1) and (2). When thearbitration option is selected, frequency selector 962 causes the degreeof the variability in IPI for any combination of stimulation frequencieson display screen 856 as a percentage of the stimulation pulses that aredelayed, as a standard deviation in the IPI, and/or through otherdescriptive statistics.

In the illustrated embodiment, stimulation rate table 1072 includes allthe stimulation frequencies, with each of the stimulation frequenciesindicated to be (a) selected, (b) available for selection (compatible),or (c) unavailable for selection (incompatible) or available forselection after arbitration. Examples for (a), (b), and (c) areillustrated in FIG. 13 as displaying areas 1074, 1076, and 1078,respectively, in which each stimulation frequency is indicated to be oneof (a), (b), or (c) using gray scale. In other embodiments, eachstimulation frequency may be indicated to be one of (a), (b), or (c)using color, pattern, or any other visually distinguishable features. Ifthe user selects the limitation option, the stimulation frequenciesindicated to be (c), e.g., 1078, are displayed but not selectable by theuser. If the user selects the arbitration option, the stimulationfrequencies indicated to be (c), e.g., 1078, as displayed are eachselectable by the user but associated with a modification of timing(e.g., introduction of delays) in delivering the neurostimulation pulsesresulting from the arbitration. In various embodiments, stimulationfrequency module 966 causes the plurality of stimulation frequencies tobe displayed on screen 856 with each stimulation frequency visuallyindicated to be (a), (b), or (c). When the arbitration option isselected, stimulation frequency module 966 causes the plurality ofstimulation frequencies to be displayed on screen 856 with visualindications for the stimulation frequencies to which the arbitration isperformed and/or the degree to which arbitration is performed for thatcombination of stimulation frequencies.

In one embodiment, stimulation rate table 1072 allows for selection ofall stimulation frequencies, including stimulation frequencies for whichthe arbitration is performed. No stimulation frequency is unavailable instimulation rate table 1072 (i.e., all the stimulation frequencies areselectable), but the stimulation frequencies for which the arbitrationis performed are indicated in stimulation rate table 1072. In oneembodiment, the stimulation frequencies for which the arbitration isperformed are indicated with showing of the degree of resultingvariability in the IPI in stimulation rate table 1072.

In various embodiments, using stimulation rate table 1072 allows theuser to skip directly to desired stimulation frequencies without havingto pass through unwanted combinations of frequencies. Stimulation ratetable 1072 also allows the user to compare a complete list of availablecombinations of the stimulation frequencies before choosing the bestcombination.

In various embodiments, the stimulation frequencies displayed instimulation rate table 1072, as well as various other stimulationparameters, are determined based on analysis of interactions betweendifferent stimuli of the neurostimulation. An example of such differentstimuli includes neurostimulation delivered from different electrodes.FIGS. 11-14 illustrate some examples of scenarios in which interactionsbetween neurostimulation delivered from different electrodes may haveeffect on therapeutic outcome. These examples are for illustrativepurposes only, are not intended to be an exhaustive or exclusivecollection of possible scenarios, and may reflect only a portion of acomplete electrode set used in a neuromodulation therapy. In variousembodiments, the different stimuli of the neurostimulation may includespatially and/or temporally different stimuli.

In the following discussion, an active electrode refers to an electrodeselected from a plurality of electrodes in a neurostimulation systemthat is selected for delivering neurostimulation pulses in each example.In each of FIGS. 11-14, an active Electrode 1 and an active Electrode 2are illustrated. A first volume of tissue activated (VTA 1) results fromneurostimulation pulses delivered through Electrode 1. A second volumeof tissue activated (VTA 2) results from neurostimulation pulsesdelivered through Electrode 2.

VTA 1 and VTA 2 may result from neurostimulation pulses that areoverlapping, partially overlapping, or non-overlapping in time, whilethe time delays of the VTAs with respect to the target of theneurostmulation result in the target being modulated by theneurostimulation pulses through both VTA 1 and VTA 2. For example, VTA 1and VTA 2 may be non-overlapping in time, but the time delay associatedwith each of VTA 1 and VTA 2 with respect to an upstream or downstreamtarget is such that the modulation effect on the target results fromboth VTA 1 and VTA 2. When the modulation effect is undesirable, such arelationship between VTA1 and VTA2 may be warned to the user and/orprevented. When the modulation effect is desirable, such a relationshipbetween VTA 1 and VTA2 is allowed, and the relatively timing between VTA1 and VTA 2 may be adjusted or optimized for benefiting from thisrelationship. The target is modulated when a physiological response isevoked by the delivery of the neurostimulaton pulses. The modulation mayinclude, for example, supra-threshold stimulation that evokes one ormore neural action potentials or sub-threshold stimulation thatmodulates one or more characteristics of the target tissue withoutevoking an active potential.

FIG. 11 illustrates an example of partially overlapping volumes oftissue activated (VTAs) by neurostimulation pulses delivered fromdifferent electrodes. VTA 1 and VTA2 partially overlap in space and havea common volume (VTA Overlap).

FIG. 12 illustrates an example of a common neural element stimulated byneurostimulation pulses delivered from different electrodes. In thisdocument, a “common neural element” refers to an anatomic unit of thenervous system (e.g., a particular nerve or nerve branch) that isstimulated or targeted by neurostimulation energy from different sources(e.g., neurostimulation pulses delivered from different electrodes). VTA1 and VTA 2 do not spatially overlap, but each include a portion of acommon neural element such that the common neural element may bemodulated by neurostimulation pulses delivered through both Electrode 1and Electrode 2.

FIG. 13 illustrates an example of a common upstream or downstream targetstimulated by neurostimulation pulses delivered from differentelectrodes. VTA 1 and VTA 2 do not spatially overlap, but each include aportion of a neural element connected to a common upstream or downstreamtarget such that the upstream or downstream target may be stimulated byneurostimulation pulses delivered through both Electrode 1 and Electrode2. In the illustrated example, the final target of the neurostimulation,which may be upstream or downstream from VTA 1 and VTA 2, is coupled toVTA 1 and VTA 2 through neural elements and intermediate targets. Theintermediate targets may each be modulated by the neurostimulationpulses delivered through Electrode 1 only, Electrode 2 only, or bothElectrode 1 and Electrode 2. The common final target may be modulated bythe neurostimulation pulses through both Electrode 1 and Electrode 2.

FIG. 14 illustrates an example of a common anatomical target stimulatedby neurostimulation pulses delivered from different electrodes. VTA 1and VTA 2 do not spatially overlap, but each include a portion of acommon anatomical target such that the anatomical target may bemodulated by neurostimulation pulses delivered through both Electrode 1and Electrode 2.

In various embodiments, the VTAs may be estimated based on, for example,visualization of Stimulation Field Models (SFMs). Combinations ofstimulation parameters that do not result in overlapping SFMs are notsubject to the rate rule because they do not stimulate the same volumeof tissue. Combinations of stimulation parameters that do result inoverlapping SFMs are limited to certain compatible combinations ofrates. Thus, values of stimulation parameters are limited such thatinteractions between neurostimulation pulses are managed according to aset of desirable outcomes.

In various embodiments, all target tissue to be modulated byneurostimulation is modulated at the same rate (stimulation frequency)by all stimulating fields. In other words, no portion of the targettissue should be stimulated at a different rate (resulting fromdifferent stimulation frequencies applied for different stimulationfields). The amount of stimulation from each active electrode may belimited, given the amount of stimulation from other active electrodes,such that the VTAs from each active electrode do not overlap. In variousother embodiments, instead of avoiding overlap of the VTAs, some amountof overlap of the VTAs is permitted according to some rules. Forexample, the rules may ensure that total overlapping VTA amount is lessthan a given threshold, or total amount of secreted/emitted/dispersedneurotransmitter or compound is less than or greater than a thresholds.

FIG. 15 illustrates an embodiment of a stimulation parameter module1560, which represents an embodiment of stimulation parameter module960. Stimulation parameter module 1560 includes a parameter selector1562, an effect analyzer, and a rule-based parameter generator 1564.Stimulation parameter module 1560 allows for setting values for aplurality of waveform parameters defining a stimulation waveformaccording to which the neurostimulation is to be delivered. In oneembodiment, stimulation parameter module 1560 allows for setting valuesfor a plurality of waveform parameters defining a stimulation waveformaccording to which neurostimulation pulses are to be delivered using aset of active electrodes selected from a plurality of electrodes such asthe electrode sets or arrays discussed above in this document. Theplurality of waveform parameters includes one or more user-adjustableparameters.

Parameter selector 1562 can present a plurality of values for eachparameter of the one or more user-adjustable parameters on displayscreen 856 and allow the user to select a value for each parameter fromthe plurality of values presented on display screen 856. In oneembodiment, parameter selector 1562 includes frequency selector 962. Invarious embodiments, the plurality of values can be presented as a valuetable, such as stimulation rate table 1072, and/or presented as one ormore value ranges.

Effect analyzer 1566 can determine an interactive effect of differentstimuli of the neurostimulation. The interactive effect is a modulationof a tissue site or circuit resulting from more than one stimulus of theneurostimulation. The different stimuli may include stimuli delivered indifferent spatial and temporal manners. When the neurostimulation isdelivered as electrical pulses, the stimuli can include a pulse or agroup of pulses, and the different stimuli can include pulses or groupsof pulses defined by different spatial parameters (e.g., selection ofactive electrodes) and/or different temporal parameters (e.g., stream ofpulses delivered through different timing channel each associated with aset of one or more active electrodes). Effect analyzer 1566 candetermine the interactive effect of, for example, pulses delivered fromone or more active electrodes of the set of active electrodes. Invarious embodiments, the effect is determined using physiologicalmodeling and/or other means allowing for estimation of amount ofmodulation of a target of the neurostimulation resulting from deliveryof neurostimulation pulses from different active electrodes and/ordifferent timing channels. In various embodiments, effect analyzer 1566can determine volumes of tissue activated (VTAs) each associated astimulus of the different stimuli of the neurostimulation. In oneembodiment, effect analyzer 1566 can determine VTAs each associated withan active electrode of the set of active electrodes through which theneurostimulation pulses are delivered. In one embodiment, effectanalyzer 1566 estimates the VTAs using one or more biological models. Inone embodiment, effect analyzer 1566 estimates the VTAs usingstimulation field models (SFMs). In various embodiments, effect analyzer1566 computes the VTAs using modeling without any patient-specificinformation that allows for customization of the plurality of waveformparameters for each individual patient. In various other embodiments,effect analyzer 1566 computes the VTAs using modeling andpatient-specific information such as patient demographic information,indication information, magnetic resonance imaging (MRI), computerizedtomography (CT), diffusion tensor imaging (DTI), other imaging data,bloodwork data, or other patient-specific data, which may modulate thesize, shape, location, extend, distribution, etc., of the VTAs, or ofother parameters used to interlock the waveform parameters.

In various embodiments, a VTA, also referred to as volume of activation(VOA), may be estimated for a set of stimulation parameters based onmodeling of electrodes and tissue, for predicting effects ofneurostimulation. Examples of such modeling and VTA estimation arediscussed in U.S. Pat. No. 8,190,250 B2, entitled “SYSTEM AND METHOD FORESTIMATING VOLUME OF ACTIVATION IN TISSUE”, U.S. Pat. No. 8,706,250 B2,entitled “NEUROSTIMULATION SYSTEM FOR IMPLEMENTING MODEL-BASED ESTIMATEOF NEUROSTIMULATION EFFECTS”, U.S. Pat. No. 8,934,979 B2, entitled“NEUROSTIMULATION SYSTEM FOR SELECTIVELY ESTIMATING VOLUME OF ACTIVATIONAND PROVIDING THERAPY”, U.S. Patent Application Publication No.2014/0122379 A1, entitled “SYSTEMS AND METHODS FOR VOA MODEL GENERATIONAND USE”, all assigned to Boston Scientific Neuromodulation Corporation,which are incorporated by reference herein in their entirety.

Parameter generator 1564 can select a rate rule from a plurality of raterules based on the estimated interactive effect and to generate theplurality of values for each parameter of the one or moreuser-adjustable parameters according to the selected rate rule. Anexample for the rate rule includes the cumulative rate per lead rulediscussed above. In one embodiment, parameter generator 1564 can selecta rate rule from a plurality of rate rules based on the VTAs andgenerate the plurality of values for each parameter of the one or moreuser-adjustable parameters according to the selected rate rule. Invarious embodiments, parameter generator 1564 generates the plurality ofvalues by adjusting existing values or value ranges, such as defaultvalues or value ranges.

In this document, a “rate rule” includes a rule that governs orrestricts how one or more stimulation rates can be allowed (e.g.,programmed) based on one or more interactive effects of differentstimuli delivered at the one or more stimulation rates. A “stimulationrate” for neurostimulation can refer to the number of cycles per second.That is, there is a single unit of time and a single bolus of phases ofstimulation within that unit (e.g., a first phase, or stimulation phase,defined by an amplitude and pulse width, followed by a second phase, orrecharge phase, of opposite polarity to the first phase to recover thecharges injected in the first phase. The stimulation rate can thereforebe considered as a duty cycle, where a fraction is defined such that thenumerator is the duration of time where charge is being moved by thesystem (injected/withdrawn), and the denominator is the total durationof the cycle (e.g., 1 second). With new types of stimulation, there canbe additional hierarchies of duty cycles, such that a first rate (e.g.,130 Hz for DB) may be modulated in an on-and-off fashion by additional,longer-duration cycles (e.g., 1 Hz, i.e., 1 second on, 1 second off, andso on). These durations can be symmetric, (e.g., 1 second on, 1 secondoff) or asymmetric (e.g., 1 second on, 3 seconds off). A plurality ofsuch modulations can be stacked. A stimulation approach referred to asCoordinated Reset stimulation involves multiple of these hierarchies ofduty cycles (stimulation rates). For example, stimulation bursts of 130Hz can be alternated between fields for durations of 77 ms. A collectionof 10 bursts may be called a Cycle, and Cycles played for 2 on (154 ms),10 off (770 ms) may each be called a micro-schedule, wherebymirco-scheduled stimulation may be on for 2 hours (a period called abolus or dose) followed by off for 10 hours, such that a 24-hourrepeating pattern is defined. The stimulation rates at these varioushierarchies are implicated in the present subject matter. Certain of thelevels of the hierarchy are more or less amenable to analysis usingSFMs, but all levels can be integrated into various biological models.

Examples of the rate rules include, but are not limited to, determiningthe plurality of values for each parameter of the one or moreuser-adjustable parameters:

-   -   for controlling an extent to which the VTAs spatially overlap;        -   such that the VTAs do not spatially overlap;        -   such that the VTAs have an overlapping volume that is under            a specified volume;        -   such that the VTAs have an overlapping volume that exceeds a            specified volume;    -   for controlling an extent to which a common anatomical target is        modulated by different stimuli of the neurostimulation;        -   such that the common anatomical target indicated by the VTAs            is not modulated by different stimuli of the            neurostimulation;        -   such that the common anatomical target indicated by the VTAs            is modulated by different stimuli of the neurostimulation;    -   for controlling an extent to which a common neural element        indicated by the VTAs is modulated by different stimuli of the        neurostimulation;        -   such that the common neural element indicated by the VTAs is            not activated by different stimuli of the neurostimulation;        -   such that the common neural element indicated by the VTAs is            modulated by different stimuli of the neurostimulation;        -   such that the common neural element indicated by the VTAs is            modulated to a measureable amount by different stimuli of            the neurostimulation;            -   the measurable amount within a specified range;            -   the measurable amount below a threshold amount;            -   the measurable amount above a threshold amount;    -   for controlling an extent to which a common upstream or        downstream tissue target indicated by the VTAs is modulated by        different stimuli of the neurostimulation;        -   such that the common upstream or downstream tissue target            indicated by the VTAs is not modulated by different stimuli            of the neurostimulation;        -   such that the common upstream or downstream tissue target            indicated by the VTAs is modulated by different stimuli of            the neurostimulation;    -   for controlling an extent to which a common physiological target        indicated by the VTAs is not modulated by different stimuli of        the neurostimulation;        -   such that a common physiological target indicated by the            VTAs is not modulated by different stimuli of the            neurostimulation;        -   such that a common physiological target indicated by the            VTAs is modulated by different stimuli of the            neurostimulation.            In various embodiments, the different stimuli of the            neurostimulation may include spatially and/or temporally            different stimuli. In the example of neurostimulation            pulses, spatially different stimuli may include pulses            delivered from different electrodes, and temporally            different stimuli may include pulses delivered at different            times or pulses of different pulse groups defined by            different set of temporal parameters. In various            embodiments, two or more of such rate rules that are not            mutually exclusive may be applied simultaneously. In various            embodiments, such rate rules may be implemented as decision            trees or state machines for determining the plurality of            values for each user-adjustable parameter of the plurality            of waveform parameters.

FIG. 16 illustrates a flow chart of a method 1670 for determiningstimulation parameter values based on estimated effects ofneurostimulation pulses delivered through different electrodes. In oneembodiment, method 1670 is performed by system 100, including itsvarious embodiments as discussed in this document. In variousembodiments, the neurostimulation pulses are delivered according to astimulation waveform to a set of active electrodes selected from aplurality of electrodes of a neurostimulation system. The stimulationwaveform is defined by a plurality of waveform parameters including oneor more user-adjustable parameters. While neurostimulation pulses arediscussed as a specific example of stimuli of neurostimulation, method1670 may be applied using any form of neurostimulation energy andstimuli in various embodiments.

At 1671, VTAs each associated with an active electrode of the set ofactive electrodes are determined. In various embodiments, the VTAs areestimated using one or more biological models capable of modeling apatient's physiological response to various stimulation parameters. Anexample is to estimate the VTAs using SFMs.

At 1672, a rate rule is selected from a plurality of rate rules based onthe VTAs. The rate rules each relate values of the one or moreuser-adjustable parameters to a desirable therapeutic outcome.

The VTAs are discussed as a specific example of means for analyzing theeffect of neurostimulation. In various embodiments, the effect ofneurostimulation may be determined using physiological modeling and/orother means allowing for estimation of amount of modulation of a targetof the neurostimulation resulting from delivery of neurostimulationpulses from different active electrodes. In various embodiments, aneffect of energy of the neurostimulation delivered from two or moreactive electrodes of the set of active electrodes is estimated at 1671,and a rate rule is selected from a plurality of rate rules based on theestimated effect at 1672.

At 1673, a plurality of values is generated for each user-adjustableparameter according to the selected rate rule. Examples of the raterules are discussed above. In various embodiments, the plurality ofvalues for each user-adjustable parameter is determined to control anextent to which the VTAs overlap. The extent may be specified as nooverlap, a permissible overlap up to a certain threshold, or apermissible overlap of at least a certain threshold. In variousembodiments, the plurality of values for each user-adjustable parameteris determined to control an extent to which a common target indicated bythe VTAs is modulated by different stimuli of the neurostimulation, suchas more than one pulse of the neurostimulation pulses. The extent may bemeasured by one or more sensed or observed parameters and specified bythreshold values of these parameters.

At 1674, the plurality of values generated for each user-adjustableparameter is presented on a display screen. In one embodiment, theplurality of values is presented as a table listing all the values. Inanother embodiment, the plurality of values is presented as one or morevalues ranges. On example for the one or more user-adjustable parametersis the stimulation frequency (rate), whose values may be presented in astimulation rate table such as stimulation rate table 1072 asillustrated in FIG. 10 and discussed above with reference to FIG. 10.

At 1675, the user is allowed to select a value for each user-adjustableparameter from the plurality of values presented on the display screen.At 1676, neurostimulation pulses are delivered according to thestimulation waveform defined by the plurality of waveform parametersincluding the one or more user-adjustable parameters, using the value(s)of the one or more user-adjustable parameters selected by the user at1675. In various embodiments, the neurostimulation pulses are deliveredfrom an implantable, external, or percutaneous stimulation system thatincludes a stimulation device programmed with the plurality of waveformparameters. After selecting value(s) for the one or more user-adjustableparameters at 1675, the user may program the stimulation device to startthe delivery of the neurostimulation pulses at 1676.

It is to be understood that the above detailed description is intendedto be illustrative, and not restrictive. Other embodiments will beapparent to those of skill in the art upon reading and understanding theabove description. The scope of the invention should, therefore, bedetermined with reference to the appended claims, along with the fullscope of equivalents to which such claims are entitled.

What is claimed is:
 1. A system for delivering neurostimulation to apatient and controlling the delivery of the neurostimulation by a user,the system comprising: a display; and an interface control circuitconfigured to define a stimulation waveform according to which theneurostimulation is to be delivered, the stimulation waveform defined bya plurality of waveform parameters including one or more user-adjustableparameters, the interface control circuit including: a parameterselector configured to present a plurality of values for each parameterof the one or more user-adjustable parameters on the display and allowthe user to select a value for each parameter from the presentedplurality of values; an effect analyzer configured to estimate aninteractive effect of different stimuli of the neurostimulation; and aparameter generator configured to select a rate rule from a plurality ofrate rules based on the estimated interactive effect and to generate theplurality of values for each parameter of the one or moreuser-adjustable parameters according to the selected rate rule.
 2. Thesystem of claim 1, wherein the effect analyzer is configured todetermine volumes of tissue activated (VTAs) each associated with astimulus of the different stimuli, and the parameter generator isconfigured to select the rate rule from the plurality of rate rulesbased on the VTAs.
 3. The system of claim 2, further comprising: aprogramming control circuit configured to generate a plurality ofstimulation parameters controlling delivery of the neurostimulationaccording to the stimulation waveform; and a user interface coupled tothe programming control circuit and including the display and theinterface control circuit.
 4. The system of claim 2, wherein theparameter selector is configured to present the plurality of values foreach parameter of the one or more user-adjustable parameters on thedisplay as one or more value ranges and allow the user to select a valuefor each parameter from the one or more value ranges.
 5. The system ofclaim 2, wherein the effect analyzer is configured to determine the VTAsusing one or more biological models.
 6. The system of claim 2, whereinthe effect analyzer is configured to determine the VTAs usingstimulation field models (SFMs).
 7. The system of claim 2, wherein theeffect analyzer is configured to determine the VTAs usingpatient-specific information related to one or more of size, shape,location, extent, or distribution of each of the VTAs.
 8. The system ofclaim 2, wherein the parameter generator is configured to generate theplurality of values for each parameter of the one or moreuser-adjustable parameters such that the VTAs do not spatially overlap.9. The system of claim 2, wherein the parameter generator is configuredto generate the plurality of values for each parameter of the one ormore user-adjustable parameters such that the VTAs have an overlappingvolume that is within a specified range.
 10. The system of claim 2,wherein the parameter generator is configured to generate the pluralityof values for each parameter of the one or more user-adjustableparameters for controlling an extent to which a common anatomical targetindicated by the VTAs is modulated by the different stimuli of theneurostimulation.
 11. The system of claim 2, wherein the parametergenerator is configured to generate the plurality of values for eachparameter of the one or more user-adjustable parameters for controllingan extent to which a common neural element indicated by the VTAs ismodulated by the different stimuli of the neurostimulation.
 12. Thesystem of claim 2, wherein the parameter generator is configured togenerate the plurality of values for each parameter of the one or moreuser-adjustable parameters for controlling an extent to which a commondownstream tissue target indicated by the VTAs is modulated by thedifferent stimuli of the neurostimulation.
 13. The system of claim 2,wherein the parameter generator is configured to generate the pluralityof values for each parameter of the one or more user-adjustableparameters for controlling an extent to which a common physiologicaltarget indicated by the VTAs is modulated by the different stimuli ofthe neurostimulation.
 14. The system of claim 2, wherein the parameterselector comprises a frequency selector configured to allow to user toselect of a stimulation frequency from a plurality of stimulationfrequencies.
 15. The system of claim 14, wherein the frequency selectoris configured to present on the display a plurality of stimulationfrequencies associated with each area of the plurality of areas ofstimulation, and to receive a selection of a stimulation frequency fromthe presented plurality of stimulation frequencies for that area of theplurality of areas of stimulation.
 16. A method for deliveringneurostimulation to a patient, the method comprising: delivering theneurostimulation according to a stimulation waveform defined by aplurality of waveform parameters including one or more user-adjustableparameters; estimating an interactive effect of different stimuli of theneurostimulation; selecting a rate rule from a plurality of rate rulesbased on the estimated interactive effect; generating a plurality ofvalues for each parameter of the one or more user-adjustable parametersaccording to the selected rate rule; presenting the plurality of valuesfor each parameter of the one or more user-adjustable parameters on adisplay; and allowing a user to select a value for each parameter of theone or more user-adjustable parameters from the plurality of valuespresented on the display.
 17. The method of claim 16, wherein estimatingthe interactive effect comprises determining volumes of tissue activated(VTAs) each associated with a stimulus of the different stimuli of theneurostimulation, and selecting the rate rule comprises selecting therate rule from the plurality of rate rules based on the VTAs.
 18. Themethod of claim 17, wherein generating the plurality of values for eachparameter of the one or more user-adjustable parameters according to theselected rate rule comprises determining the plurality of values tocontrol an extent to which the VTAs spatially overlap.
 19. The method ofclaim 17, wherein generating the plurality of values for each parameterof the one or more user-adjustable parameters according to the selectedrate rule comprises determining the plurality of values to control anextent to which a common target indicated by the VTAs is modulated bythe different stimuli of the neurostimulation.
 20. The method of claim17, wherein presenting the plurality of values for each parametercomprises presenting a plurality of stimulation frequencies, andallowing the user to select the value for each parameter comprisesallowing the user to select a stimulation frequency from the presentedplurality of stimulation frequencies.